Is FBXO7 p.Arg360His (c.1079G>A) pathogenic?

FBXO7 p.Arg360His (c.1079G>A) is classified Conflicting classifications of pathogenicity in FBXO7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-02). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with FBXO7 p.Arg360His (c.1079G>A)?

FBXO7 p.Arg360His (c.1079G>A) is associated with Inborn genetic diseases, parkinsonian-pyramidal syndrome (ClinVar).

How common is FBXO7 p.Arg360His (c.1079G>A) in the general population?

FBXO7 p.Arg360His (c.1079G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about FBXO7 p.Arg360His (c.1079G>A)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

FBXO7 p.Arg360His

c.1079G>A · rs111604607 · VCV2383243

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP -4.9, phastCons 0.41
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	16.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00551% 89/1,614,058 alleles · ultra-rare exomes 80/1,461,806 · genomes 9/152,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
African / African-American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0256%	3,907
South Asian	0.00439%	22,766
Admixed American	0.00333%	30,008
European (non-Finnish)	0.00331%	30,256

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FBXO7
Protein: p.Arg360His
Coding: c.1079G>A
MANE Select: NM_012179
dbSNP: rs111604607
Type: single nucleotide variant
Location: chr22:32493216 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.13 · 2 PDB
Residue 360: the f-box domain

Full FBXO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: parkinsonian-pyramidal syndrome

Similar variants

FBXO7 p.Arg360Cys Uncertain significance ★ ⚠ same residue
FBXO7 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg381Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg498Ter Pathogenic ★★ same condition
FBXO7 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Thr22Met Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fbxo7-p-arg360his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown